Topical patch vaccines target antigen to cutaneous dendritic cells efficiently inducing potent cell mediated immune responses (132.19)

Abstract

Abstract The skin contains a high density of accessible dendritic cells making it an attractive target for vaccine delivery. However, the remarkable barrier function of the skin continues to present a formidable physical obstacle to cutaneous vaccine design. To selectively overcome this obstacle, we evaluated the capacity of dissolving microneedle arrays (MNAs) to deliver protein vaccines to the skin and skin DCs. In initial experiments, biocompatible solid MNAs were fabricated with integrated particulate tracers. Image analysis demonstrated that these MNAs effectively penetrated both mouse and human skin. Further, following patch immunization labeled particulates were identified in dendritic cells in human and murine skin, and in the draining lymph nodes of immunized animals. To evaluate immunogenicity, we incorporated OVA as a soluble (sOVA) or particulate (pOVA) model protein antigen into fabricated patches, and evaluated CTL responses in immunized animals. Patch delivery of low doses of either sOVA or pOVA efficiently induced potent CTL responses comparable to those generated by optimized gene gun based immunization. Taken together, these results demonstrate the feasibility of antigen delivery for cutaneous immunization, and support the development of topical patch vaccines as an efficient and potent strategy for protein antigen based immunization. Funded by NIH.